Cys-Arg-Lys-Arg-Leu-Asp-Arg-Asn-Cys-glycol chitosan-Cy5.5 nanoparticles

Optical fluorescence imaging is increasingly being used to monitor biological functions of specific targets in small Animals (1, 2). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–700 nm) are used. Near-infrared (NIR) fluorescence (700–1,000 nm) detection avoids the background fluorescence interference of natural biomolecules, providing a high contrast between target and background tissues in small Animals. NIR fluorophores have wider dynamic range and minimal background fluorescence as a result of reduced scattering compared with visible fluorescence detection. NIR fluorophores also have high sensitivity, attributable to low background fluorescence, and high extinction coefficients, which provide high quantum yields. The NIR region is compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is a non-invasive alternative to radionuclide imaging in small Animals.

Endothelial cells are important cells in inflammatory responses (3, 4). Bacterial lipopolysaccharide, virus, inflammation, and tissue injury increase the secretion of tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and Other cytokines and chemokines. Emigration of leukocytes from blood is dependent on their ability to adhere to endothelial cell surfaces. Inflammatory mediators and cytokines induce chemokine secretion from endothelial cells and Other vascular cells and increase their expression of cell-surface adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, integrins, and selectins. Chemokines are chemotactic to leukocytes toward sites of inflammation and tissue injury. During atherogenic conditions, lipid deposits on the endothelial cell surfaces of aorta and inflammatory cells lead to development of atherosclerotic plaques (5), which may erode and rupture.

Interleukin-4 (IL-4) is a lymphokine capable of inducing T and B cell differentiation (6). IL-4 Receptor (IL-4R) is also found on endothelial cells, macrophages, and smooth muscle cells of atherosclerotic plaques (7). The atherosclerotic plaque-homing peptide (AP) Cys-Arg-Lys-Arg-Leu-Asp-Arg-Asn-Cys (CRKRLDRNC) has been identified using phage display screening (7). Park et al. (8) prepared Cy5.5- and AP-tagged nanoparticles (NPs) using hydrophobically modified glycol chitosan (HGC) for use in imaging atherosclerotic plaques. Cy5.5 is a NIR Fluorescent Dye with an absorbance maximum at 675 nm and an emission maximum at 694 nm with a high extinction coefficient of 250,000 M^-1cm^-1.